Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans

In mammals, the neuropeptide vasopressin is a key molecule for complex emotional and social behaviours. Two microsatellite polymorphisms, RS1 and RS3, near the promoter of AVPR1A , encoding the receptor subtype most heavily implicated in behaviour regulation, have been linked to autism and behaviour...

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Published in	Molecular psychiatry Vol. 14; no. 10; pp. 968 - 975
Main Authors	Meyer-Lindenberg, A, Kolachana, B, Gold, B, Olsh, A, Nicodemus, K K, Mattay, V, Dean, M, Weinberger, D R
Format	Journal Article
Language	English
Published	London Nature Publishing Group UK 01.10.2009 Nature Publishing Group
Subjects	Adult Alleles Amygdala Amygdala (Brain) Amygdala - physiology Arginine Vasopressin - genetics Autism Autistic Disorder - genetics Behavioral Sciences Biological Psychology Brain Cell receptors Emotional behavior Facial Expression Female Genetic aspects Genetic diversity Genetic Variation Health aspects Humans Magnetic Resonance Imaging Male Medicine Medicine & Public Health Microsatellite Repeats Neuroimaging Neurosciences original-article Personality - genetics Personality traits Pharmacotherapy Physiological aspects Psychiatry Receptors, Vasopressin - genetics Risk factors Vasopressin United States fMRI AVPR1A autism vasopressin neuroimaging
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Abstract	In mammals, the neuropeptide vasopressin is a key molecule for complex emotional and social behaviours. Two microsatellite polymorphisms, RS1 and RS3, near the promoter of AVPR1A , encoding the receptor subtype most heavily implicated in behaviour regulation, have been linked to autism and behavioural traits. However, the impact of these variants on human brain function is unknown. Here we show that human amygdala function is strongly associated with genetic variation in AVPR1A . Using an imaging genetics approach in a sample of 121 volunteers studied with an emotional face-matching paradigm, we found that differential activation of amygdala is observed in carriers of risk alleles for RS3 and RS1. Alleles in RS1 previously reported to be significantly over- and undertransmitted to autistic probands showed opposing effects on amygdala activation. Furthermore, we show functional difference in human brain between short and long repeat lengths that mirror findings recently obtained in a corresponding variant in voles. Our results indicate a neural mechanism mediating genetic risk for autism through an impact on amygdala signalling and provide a rationale for exploring therapeutic strategies aimed at abnormal amygdala function in this disorder.
AbstractList	In mammals, the neuropeptide vasopressin is a key molecule for complex emotional and social behaviours. Two microsatellite polymorphisms, RS1 and RS3, near the promoter of AVPR1A, encoding the receptor subtype most heavily implicated in behaviour regulation, have been linked to autism and behavioural traits. However, the impact of these variants on human brain function is unknown. Here we show that human amygdala function is strongly associated with genetic variation in AVPR1A. Using an imaging genetics approach in a sample of 121 volunteers studied with an emotional face-matching paradigm, we found that differential activation of amygdala is observed in carriers of risk alleles for RS3 and RS1. Alleles in RS1 previously reported to be significantly over- and undertransmitted to autistic probands showed opposing effects on amygdala activation. Furthermore, we show functional difference in human brain between short and long repeat lengths that mirror findings recently obtained in a corresponding variant in voles. Our results indicate a neural mechanism mediating genetic risk for autism through an impact on amygdala signalling and provide a rationale for exploring therapeutic strategies aimed at abnormal amygdala function in this disorder. In mammals, the neuropeptide vasopressin is a key molecule for complex emotional and social behaviours. Two microsatellite polymorphisms, RS1 and RS3, near the promoter of AVPR1A, encoding the receptor subtype most heavily implicated in behaviour regulation, have been linked to autism and behavioural traits. However, the impact of these variants on human brain function is unknown. Here we show that human amygdala function is strongly associated with genetic variation in AVPR1A. Using an imaging genetics approach in a sample of 121 volunteers studied with an emotional face-matching paradigm, we found that differential activation of amygdala is observed in carriers of risk alleles for RS3 and RS1. Alleles in RS1 previously reported to be significantly over- and undertransmitted to autistic probands showed opposing effects on amygdala activation. Furthermore, we show functional difference in human brain between short and long repeat lengths that mirror findings recently obtained in a corresponding variant in voles. Our results indicate a neural mechanism mediating genetic risk for autism through an impact on amygdala signalling and provide a rationale for exploring therapeutic strategies aimed at abnormal amygdala function in this disorder.In mammals, the neuropeptide vasopressin is a key molecule for complex emotional and social behaviours. Two microsatellite polymorphisms, RS1 and RS3, near the promoter of AVPR1A, encoding the receptor subtype most heavily implicated in behaviour regulation, have been linked to autism and behavioural traits. However, the impact of these variants on human brain function is unknown. Here we show that human amygdala function is strongly associated with genetic variation in AVPR1A. Using an imaging genetics approach in a sample of 121 volunteers studied with an emotional face-matching paradigm, we found that differential activation of amygdala is observed in carriers of risk alleles for RS3 and RS1. Alleles in RS1 previously reported to be significantly over- and undertransmitted to autistic probands showed opposing effects on amygdala activation. Furthermore, we show functional difference in human brain between short and long repeat lengths that mirror findings recently obtained in a corresponding variant in voles. Our results indicate a neural mechanism mediating genetic risk for autism through an impact on amygdala signalling and provide a rationale for exploring therapeutic strategies aimed at abnormal amygdala function in this disorder. In mammals, the neuropeptide vasopressin is a key molecule for complex emotional and social behaviours. Two microsatellite polymorphisms, RS1 and RS3, near the promoter of AVPR1A , encoding the receptor subtype most heavily implicated in behaviour regulation, have been linked to autism and behavioural traits. However, the impact of these variants on human brain function is unknown. Here we show that human amygdala function is strongly associated with genetic variation in AVPR1A . Using an imaging genetics approach in a sample of 121 volunteers studied with an emotional face-matching paradigm, we found that differential activation of amygdala is observed in carriers of risk alleles for RS3 and RS1. Alleles in RS1 previously reported to be significantly over- and undertransmitted to autistic probands showed opposing effects on amygdala activation. Furthermore, we show functional difference in human brain between short and long repeat lengths that mirror findings recently obtained in a corresponding variant in voles. Our results indicate a neural mechanism mediating genetic risk for autism through an impact on amygdala signalling and provide a rationale for exploring therapeutic strategies aimed at abnormal amygdala function in this disorder. In mammals, the neuropeptide vasopressin is a key molecule for complex emotional and social behaviours. Two microsatellite polymorphisms, RS1 and RS3, near the promoter of AVPR1A, encoding the receptor subtype most heavily implicated in behaviour regulation, have been linked to autism and behavioural traits. However, the impact of these variants on human brain function is unknown. Here we show that human amygdala function is strongly associated with genetic variation in AVPR1A. Using an imaging genetics approach in a sample of 121 volunteers studied with an emotional face-matching paradigm, we found that differential activation of amygdala is observed in carriers of risk alleles for RS3 and RS1. Alleles in RS1 previously reported to be significantly over- and undertransmitted to autistic probands showed opposing effects on amygdala activation. Furthermore, we show functional difference in human brain between short and long repeat lengths that mirror findings recently obtained in a corresponding variant in voles. Our results indicate a neural mechanism mediating genetic risk for autism through an impact on amygdala signalling and provide a rationale for exploring therapeutic strategies aimed at abnormal amygdala function in this disorder. doi:10.1038/mp.2008.54; published online 20 May 2008 Keywords: vasopressin; AVPR1A; fMRI; neuroimaging; autism
Audience	Academic
Author	Nicodemus, K K Dean, M Kolachana, B Olsh, A Meyer-Lindenberg, A Gold, B Mattay, V Weinberger, D R
AuthorAffiliation	5 Human Genetics Section, Laboratory of Genomic Diversity, Center for Cancer Research, NCI-Frederick, Frederick, MD, USA 4 Central Institute of Mental Health, Mannheim, Germany 3 Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, National Institute for Mental Health, NIH, DHHS, Bethesda, MD, USA 1 Unit for Systems Neuroscience in Psychiatry, National Institute for Mental Health, NIH, DHHS, Bethesda, MD, USA 2 Neuroimaging Core Facility, National Institute for Mental Health, NIH, DHHS, Bethesda, MD, USA
AuthorAffiliation_xml	– name: 3 Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, National Institute for Mental Health, NIH, DHHS, Bethesda, MD, USA – name: 2 Neuroimaging Core Facility, National Institute for Mental Health, NIH, DHHS, Bethesda, MD, USA – name: 1 Unit for Systems Neuroscience in Psychiatry, National Institute for Mental Health, NIH, DHHS, Bethesda, MD, USA – name: 4 Central Institute of Mental Health, Mannheim, Germany – name: 5 Human Genetics Section, Laboratory of Genomic Diversity, Center for Cancer Research, NCI-Frederick, Frederick, MD, USA
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Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-1 content type line 23 These authors contributed equally to this work.
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PublicationTitle	Molecular psychiatry
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Publisher	Nature Publishing Group UK Nature Publishing Group
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Snippet	In mammals, the neuropeptide vasopressin is a key molecule for complex emotional and social behaviours. Two microsatellite polymorphisms, RS1 and RS3, near the...
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SubjectTerms	Adult Alleles Amygdala Amygdala (Brain) Amygdala - physiology Arginine Vasopressin - genetics Autism Autistic Disorder - genetics Behavioral Sciences Biological Psychology Brain Cell receptors Emotional behavior Facial Expression Female Genetic aspects Genetic diversity Genetic Variation Health aspects Humans Magnetic Resonance Imaging Male Medicine Medicine & Public Health Microsatellite Repeats Neuroimaging Neurosciences original-article Personality - genetics Personality traits Pharmacotherapy Physiological aspects Psychiatry Receptors, Vasopressin - genetics Risk factors Vasopressin
Title	Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans
URI	https://link.springer.com/article/10.1038/mp.2008.54 https://www.ncbi.nlm.nih.gov/pubmed/18490926 https://www.proquest.com/docview/221238518 https://www.proquest.com/docview/2645751253 https://www.proquest.com/docview/21235759 https://www.proquest.com/docview/733849088 https://pubmed.ncbi.nlm.nih.gov/PMC2754603
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